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Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors. Nat Commun 2015 Jan 13;6:6077



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-84923079683   79 Citations


Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection.

Author List

Hopf TA, Morinaga S, Ihara S, Touhara K, Marks DS, Benton R


David S. Marks MD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acids
Evolution, Molecular
Receptors, Odorant